The vast majority of histone methyltransferases and demethylases were identified in the 21st century but their biological functions are poorly understood. We use adipogenesis as a model system to study the roles of histone methyltransferases and demethylases, and the dynamics of site-specific histone methylation, in regulation of gene expression and cell differentiation. We are interested in methylations on K4, K9 and K27 of histone H3 (H3K4, H3K9 and H3K27, respectively). The Polycomb repressive complex 2 (PRC2) is a major regulator of animal development. PRC2 represses gene expression mainly through its enzymatic subunit Ezh2-mediated tri-methylation on H3K27 (H3K27me3). Using Ezh2 conditional KO preadipocytes, we report that Ezh2 and its H3K27 methyltransferase activity are required for adipogenesis and that Ezh2 constitutively represses Wnt genes to facilitate adipogenesis (Wang L, PNAS 2010). Histone methyltransferase G9a is responsible for H3K9 di-methylation (H3K9me2), an epigenetic mark for gene repression. Using G9a conditional KO preadipocytes, we report recently that G9a represses PPAR&#947; expression and adipogenesis. G9a regulates both positive and negative master regulators of adipogenesis: G9a represses PPAR&#947; expression dependent on its H3K9 methyltransferase activity while promotes Wnt expression independent of its enzymatic activity (Wang L, EMBO J 2013). Together with our reports that H3K4me1/2 methyltransferases MLL3/MLL4 are required for PPAR&#947; and C/EBP&#945; expression and adipogenesis (Lee JE, eLife 2013), these findings provide an initial view of epigenetic regulation of adipogenesis, and suggest that histone methylations control expression of positive and negative master regulators of adipogenesis (reviewed in BBA 2012 and Cell & Biosci 2014).